title: Characterization of haematological parameters with bortezomib-melphalan-prednisone versus melphalan-prednisone in newly diagnosed myeloma, with evaluation of long-term outcomes and risk of thromboembolic events with use of erythropoiesis-stimulating agents: analysis of the VISTA trial.
abstract: Although haematological toxicities, such as anaemia, are common in multiple myeloma (MM), no clear consensus exists on the use and impact of erythropoiesis-stimulating agents (ESA) on outcomes in MM. This analysis characterizes haematological toxicities and associated interventions in the phase III VISTA (Velcade(®)  as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone) study of bortezomib plus melphalan/prednisone (VMP, n = 344) versus MP (n = 338) in previously untreated MM patients ineligible for high-dose therapy, and evaluates the impact of ESA use or red-blood-cell (RBC) transfusions on outcomes and thromboembolic risk. Incidence of haematological toxicities was similar with VMP and MP; similar rates of interventions and associated complications (e.g. bleeding, febrile neutropenia) were observed. Two hundred thirty three patients received ESA; 204 had RBC transfusions. Frequency of thromboembolic events was low and not affected by ESA use. Median time-to progression (TTP) was similar between ESA/non-ESA [hazard ratio: 1·03 (95% confidence interval 0·76-1·39); P = 0·8478] in both arms (VMP: 19·9/not reached; MP: 15·0/17·5 months). Three-year overall survival (OS) rates were similar between ESA/non-ESA in each arm. Patients receiving RBC transfusions had significantly shorter OS (P < 0·0001) versus non-RBC-transfusion patients. In conclusion, bortezomib did not add to melphalan haematological toxicity. Concomitant ESA use with VMP/MP in previously untreated MM patients did not adversely affect TTP or OS, or increase thromboembolic risk. However, RBC transfusion was associated with significantly shorter survival.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Richardson
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Nuriet
authors.initials: N
authors.lastname: Khuageva
authors.forename: Meletios
authors.initials: M
authors.lastname: Dimopoulos
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Martin
authors.initials: M
authors.lastname: Kropff
authors.forename: Marie-Christiane
authors.initials: MC
authors.lastname: Vekemans
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Petrucci
authors.forename: Viktor
authors.initials: V
authors.lastname: Rossiev
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Robak
authors.forename: Maria-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.forename: Kenneth
authors.initials: K
authors.lastname: Anderson
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.forename: Andrew
authors.initials: A
authors.lastname: Cakana
authors.forename: Kevin
authors.initials: K
authors.lastname: Liu
authors.forename: William
authors.initials: W
authors.lastname: Deraedt
authors.forename: Helgi
authors.initials: H
authors.lastname: van de Velde
authors.forename: Jesús F
authors.initials: JF
authors.lastname: San Miguel
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D018572:Disease-Free Survival; D017707:Erythrocyte Transfusion; D005260:Female; D006397:Hematinics / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate; D013923:Thromboembolism / Q000209:etiology / Q000401:mortality / Q000628:therapy
chemical_list: D001897:Boronic Acids; D006397:Hematinics; D011719:Pyrazines; D000069286:Bortezomib; D011239:Prednisolone; D008558:Melphalan